As a pharmaceutical composition comprising an antagonist against PGD2 receptor, a compound of the formula: wherein Y is bicyclic ring and R is phenyl etc., was described in WO 97/00853 (International publication date: Jan. 1, 1997).
On the other hand, it was disclosed that 3-oxa-derivatives were prepared as metabolically stable TXA2/PGH2 receptor antagonists in Bioorganic & Medicinal Chemistry Letters, Vol. 2, No. 9, pp. 1069-1072, 1992. The active value of the compound was only described but the metabolic stability has not been described in the literature. wherein, Z is p-fluorophenyl; Rω is benzenesulfonamino and the like.
Furthermore, it was reported in PROSTAGLANDINS, 1986, 31, 95 that ILOPROST, PGI2 mimetics was stabilized metabolically by converting to the 3-oxa-derivative. But, remaining activity of each compound was only compared under a presence of the metabolic enzyme of a rat and the metabolic stability did not mentioned.